Ethnomedicinal Uses, Phytochemistry, and Anticancer Potentials of African Medicinal Fruits: A Comprehensive Review.

Africa is home to diverse medicinal plants that have been used for generations for the treatment of several different cancers and, presently, they are gaining interest from researchers as promising approaches to cancer treatment. This review aims to provide a comprehensive review of dietary and medicinal African fruits including their traditional uses, botanical description, ethnobotanical uses, bioactive phytochemical compositions, and anticancer properties investigated to date in vitro, in vivo, and in clinical studies. Data on recent updates concerning the traditional uses and anticancer properties of these fruits were collected from a myriad of available publications in electronic databases, such as Web of Science, PubMed, ScienceDirect, Scopus, SpringerLink, and Google Scholar. The results suggest that approximately 12 native or commercially grown African fruits belonging to different plant species, including Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum, have been reported for their potential as treatment options for the management of cancer. We further found that approximately eight different fruits from native plant species from Africa, namely, Sclerocarya birrea, Dovyalis caffra, Parinari curatellifolia, Mimusops caffra, Carpobrotus edulis, Vangueria infausta, Harpephyllum caffrum, and Carissa macrocarpa, have been widely used for the traditional treatment of different ailments but somehow failed to gain the interest of researchers for their use in anticancer research. In this review, we show the potential use of various fruits as anticancer agents, such as Tribulus terrestris, Xanthium strumarium, Withania somnifera, Xylopia aethiopica, Abelmoschus esculentus, Carissa macrocarpa, Carpobrotus edulis, Syzygium cumini, Kigelia Africana, Annona muricata, Persea americana, and Punica granatum; unfortunately, not enough reported research data have been published to gain thorough mechanistic insights and clinical applications. Additionally, we discuss the possibility of the utilization of potential phytochemicals from fruits like Persea americana and Punica granatum in anticancer research, as well as future directions.

Understanding the Photodynamic Therapy Induced Bystander and Abscopal Effects: A Review.

Photodynamic therapy (PDT) is a clinically approved minimally/non-invasive treatment modality that has been used to treat various conditions, including cancer. The bystander and abscopal effects are two well-documented significant reactions involved in imparting long-term systemic effects in the field of radiobiology. The PDT-induced generation of reactive oxygen and nitrogen species and immune responses is majorly involved in eliciting the bystander and abscopal effects. However, the results in this regard are unsatisfactory and unpredictable due to several poorly elucidated underlying mechanisms and other factors such as the type of cancer being treated, the irradiation dose applied, the treatment regimen employed, and many others. Therefore, in this review, we attempted to summarize the current knowledge regarding the non-targeted effects of PDT. The review is based on research published in the Web of Science, PubMed, Wiley Online Library, and Google Scholar databases up to June 2023. We have highlighted the current challenges and prospects in relation to obtaining clinically relevant robust, reproducible, and long-lasting antitumor effects, which may offer a clinically viable treatment against tumor recurrence and metastasis. The effectiveness of both targeted and untargeted PDT responses and their outcomes in clinics could be improved with more research in this area.

Paradigm shift in future biophotonics for imaging and therapy: Miniature living lasers to cellular scale optoelectronics.

Advancements in light technology, devices and its applications have tremendously changed the facets of biomedical science and engineering to provide powerful diagnostic and therapeutic capabilities ranging from basic research to clinics. Recent novel innovations and concepts in the field of material science, biomedical optics, processing technology and nanotechnology have enabled increasingly sophisticated technologies such as cellular scale, wireless, remotely controlled micro device for in vivo integrations. This review deals with such futuristic applications of biophotonics like miniature living lasers, wireless remotely controlled implantable and cellular optoelectronics for novel imaging, diagnostic and therapeutic applications. We begin with an overview of the competency and progress in biophotonics as one of the most active frontiers in advanced analytical, diagnostic and therapeutic modalities. This is further followed by comprehensive discussion on recent advances, importance and applications, towards miniaturization size of laser to integrate into live cells as biological lasers, and wearable and implantable optoelectronic devices. Such applications form a novel biocompatible platform for intracellular sensing, cytometry and imaging devices. Further, the opportunities and possible challenges for future research directions to transform this basic research to clinical applications are also discussed.

Multi-Target Potential of Berberine as an Antineoplastic and Antimetastatic Agent: A Special Focus on Lung Cancer Treatment.

Despite therapeutic advancements, lung cancer remains the principal cause of cancer mortality in a global scenario. The increased incidence of tumor reoccurrence and progression and the highly metastatic nature of lung cancer are of great concern and hence require the investigation of novel therapies and/or medications. Naturally occurring compounds from plants serve as important resources for novel drugs for cancer therapy. Amongst these phytochemicals, Berberine, an alkaloid, has been extensively explored as a potential natural anticancer therapeutic agent. Several studies have shown the effectiveness of Berberine in inhibiting cancer growth and progression mediated via several different mechanisms, which include cell cycle arrest, inducing cell death by apoptosis and autophagy, inhibiting cell proliferation and invasion, as well as regulating the expression of microRNA, telomerase activity, and the tumor microenvironment, which usually varies for different cancer types. In this review, we aim to provide a better understanding of molecular insights of Berberine and its various derivative-induced antiproliferative and antimetastatic effects against lung cancer. In conclusion, the Berberine imparts its anticancer efficacy against lung cancers via modulation of several signaling pathways involved in cancer cell viability and proliferation, as well as migration, invasion, and metastasis.

A Review on Traditionally Used African Medicinal Plant Annickia chlorantha, Its Phytochemistry, and Anticancer Potential.

Annickia chlorantha Setten & P.J.Maas belongs to the Annonaceae family and is a multi-purpose medicinal plant, which has been extensively used for the traditional treatment option for malaria in western and central Africa. Its phytochemical composition is dominated particularly by various biologically active protoberberines and acetogenins. This review aims to provide a comprehensive review on the traditional uses, phytochemical profiles, and the toxicology of this plant from a myriad of available publications. Even after its tremendous applications against several different human ailments, this plant has been underestimated for its anticancer potential. Herein, based on the phytochemical composition, we discuss the probable mode of mechanism for its antiproliferative activity, which highlights its importance for cytotoxicity screenings against cancer cells. Additionally, this article discusses several research questions and suggests the future directions of its applications in medicinal plant-based anticancer research.

Fundamentals and applications of metal nanoparticle- enhanced singlet oxygen generation for improved cancer photodynamic therapy.

The introduction of nanotechnology in the field of Photodynamic Therapy (PDT) has proven to have great potential to overcome some of the challenges associated with traditional organic photosensitizers (PS) with respect to their solubility, drug delivery, distribution and site-specific targeting. Other focused areas in PDT involve high singlet oxygen production capability and excitability of PS by deep tissue penetrating light wavelengths. Owing to their very promising optical and surface plasmon resonance properties, combination of traditional PSs with plasmonic metallic nanoparticles like gold and silver nanoparticles results in remarkably high singlet oxygen production and extended excitation property from visible and near-infrared lights. This review summarizes the importance, fundamentals and applications of on plasmonic metallic nanoparticles in PDT. Lastly, we highlight the future prospects of these plasmonic nanoengineering strategies with or without PS combination, to have a significant impact in improving the therapeutic efficacy of cancer PDT.

Potential Application of Photosensitizers With High-Z Elements for Synergic Cancer Therapy.

The presence of heavy elements in photosensitizers (PS) strongly influences their electronic and photophysical properties, and hence, conjugation of PS with a suitable element is regarded as a potential strategy to improve their photodynamic properties. Moreover, PS conjugated to metal ion or metal complex and heavy atoms such as halogen have attracted considerable attention as promising agents for multimodal or synergistic cancer therapy. These tetrapyrrole compounds depending on the type and nature of the inorganic elements have been explored for photodynamic therapy (PDT), chemotherapy, X-ray photon activation therapy (PAT), and radiotherapy. Particularly, the combination of metal-based PS and X-ray irradiation has been investigated as a promising novel approach for treating deep-seated tumors, which in the case of PDT is a major limitation due to low light penetration in tissue. This review will summarize the present status of evidence on the effect of insertion of metal or halogen on the photophysical properties of PS and the effectiveness of various metal and halogenated PS investigated for PDT, chemotherapy, and PAT as mono and/or combination therapy.

Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases.

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer.

In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.

Enhancement of radiosensitivity of oral carcinoma cells by iodinated chlorin p6 copper complex in combination with synchrotron X-ray radiation.

The combination of synchrotron X-ray radiation and metal-based radiosensitizer is a novel form of photon activation therapy which offers the advantage of treating malignant tumors with greater efficacy and higher precision than conventional radiation therapy. In this study the anticancer cytotoxic efficacy of a new chlorophyll derivative, iodinated chlorin p6 copper complex (ICp6-Cu), combined with synchrotron X-ray radiation (8-10 keV) in two human oral cancer cell lines is explored. Pre-treatment of cells with 20 µM and 30 µM ICp6-Cu for 3 h was found to enhance the X-ray-induced cytotoxicity with sensitization enhancement ratios of 1.8 and 2.8, respectively. ICp6-Cu localized in cytoplasm, mainly in lysosomes and endoplasmic reticulum, and did not cause any cytotoxicity alone. The radiosensitization effect of ICp6-Cu accompanied a significant increase in the level of reactive oxygen species, damage to lysosomes, inhibition of repair of radiation-induced DNA double-strand breaks, increase in cell death and no significant effect on cell cycle progression. These results demonstrate that ICp6-Cu is a potential agent for synchrotron photon activation therapy of cancer.

Iodinated chlorin p6 copper complex induces anti-proliferative effect in oral cancer cells through elevation of intracellular reactive oxygen species.

We investigated the anticancer chemotoxicity of previously reported iodinated chlorin p6 copper complex (ICp6-Cu), a novel chlorophyll derivative in which copper is attached to the side chain carboxylate groups via coordination. Human oral carcinoma cells NT8e, 4451 and the non-cancerous keratinocyte HaCaT cells were treated with ICp6-Cu for 48 h in dark and cell viability, proliferation and morphological alterations were examined. ICp6-Cu showed pronounced cytotoxicity in cancer cells with IC50 ∼40 µM, whereas, the viability of HaCaT cells was not affected. Cell proliferation assay revealed that ICp6-Cu at IC50 concentration led to complete inhibition of cell proliferation in both the cell lines. Cell morphology studied by confocal microscopy showed absence of cell death via necrosis or apoptosis. Instead, the treated cells displayed distinct features of non-apoptotic death such as highly vacuolated cytoplasm, lysosomal membrane permeabilization and damage to cytoskeleton F-actin filaments. In addition, ICp6-Cu treatment led to time dependent increase in the intracellular level of reactive oxygen species (ROS) and the cytotoxicity of ICp6-Cu was significantly inhibited by pre-treatment of cells with antioxidants (glutathione and trolox). These findings revealed that ICp6-Cu is a potent chemotoxic agent which can induce cytotoxic effect in cancer cells through elevation of intracellular ROS. It is suggested that ICp6-Cu may provide tumor selective chemotoxicity by exploiting difference of redox environment in normal and cancer cells.